Precision Medicine

Cholerton, Brenna; Larson, Eric B.; Quinn, Joseph F.; Zabetian, Cyrus P.; Mata, Ignacio; Keene, C. Dirk; Flanagan, Margaret E.; Crane, Paul K.; Grabowski, Thomas J.; Montine, Kathleen S.; Montine, Thomas J.

doi:10.1016/j.ajpath.2015.12.001

Cited by 54 publications

(22 citation statements)

References 58 publications

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“…To effectively target and treat dementia associated with type 2 diabetes, such treatment would be most effective when implemented as early as possible, preferably during a latent or prodromal phase when the neuropathological changes are not yet significant enough to result in significant overt clinical symptoms (55). Importantly, both type 2 diabetes and dementia are associated with prolonged prodromal phases, and although symptoms may not be overt, current advances permit early identification of both syndromes.…”

Section: Precision Health: Early Detectionmentioning

confidence: 99%

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

et al. 2016

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IN BRIEF There has been a concurrent dramatic rise in type 2 diabetes and dementia in the United States, and type 2 diabetes shares common genetic and environmental risk factors and underlying pathology with both vascular and Alzheimer’s dementias. Given the ability to identify this at-risk population and a variety of potential targeted treatments, type 2 diabetes represents a promising focus for a precision health approach to reduce the impact of cognitive decline and dementia in older adults.

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Section: Precision Health: Early Detectionmentioning

confidence: 99%

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

et al. 2016

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“…Meaningfully subdividing a condition into distinct groups is essential to the strategy of personalized medicine 1–3 . Data are currently lacking demonstrating a scalable approach for meaningfully subdividing Alzheimer’s dementia.…”

Section: Introductionmentioning

confidence: 99%

Incidence of cognitively defined late‐onset Alzheimer's dementia subgroups from a prospective cohort study

Crane

Trittschuh

Mukherjee

et al. 2017

Alzheimer's & Dementia

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INTRODUCTION There may be biologically relevant heterogeneity within typical late-onset Alzheimer’s dementia. METHODS We analyzed cognitive data from people with incident late-onset Alzheimer’s dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. RESULTS During 32,286 person-years of follow-up, 869 people developed Alzheimer’s dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with APOE ε4, more extensive Alzheimer’s-related neuropathology, and higher proportions with other Alzheimer’s dementia genetic risk variants. DISCUSSION A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer’s dementia.

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“…Despite the huge potential of advanced systems-level approaches applied to multifactorial diseases, the reality is that evolving precision medicine initiatives for AD and other neurodegenerative diseases (1, 20–22, 41) are still missing the essential SB framework, which is key for the successful implementation and operationalization of precision medicine strategies (Figure 1). This critical issue needs to be fully corrected in order to advance healthcare towards “true precision medicine”.…”

Section: The Systems Biology (Sb) Paradigm For Complex Multifactorialmentioning

confidence: 99%

“…Even though precision medicine-based strategies for AD are being the subject of increasing attention and investigations (1, 20–22, 41), the requirement to apply systems-level methods and approaches to AD (Figure 1) is mostly underestimated or even overlooked. SB approaches towards precision medicine paradigm are urgently needed; to this aim, multidisciplinary worldwide collaborations will be required to progress from SB to translational systems medicine and public health.…”

Section: The Systems Biology (Sb) Paradigm For Complex Multifactorialmentioning

confidence: 99%

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

Hampel¹,

O’Bryant

Castrillo

et al. 2016

J Prev Alz Dis

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During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer’s disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical “one-size-fits-all” approach in drug discovery towards biomarker guided “molecularly” tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.

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Precision Medicine

Cited by 54 publications

References 58 publications

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

Incidence of cognitively defined late‐onset Alzheimer's dementia subgroups from a prospective cohort study

Precision Medicine - The Golden Gate for Detection, Treatment and Prevention of Alzheimer’s Disease

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